Figure 1.

Immunosuppressive cells in the glioma microenvironment. (A) GAMs release many cytokines that promote the malignant phenotype of GBM and maintain the high permeability of the blood–brain barrier, including TGF-β, IL-6, and IL-1β. Targeting the phagocytosis checkpoints such as CCL2/CCR2, CD47/SIRP-α, and the CSF-1/CSF-1R axis can enhance the phagocytosis of tumor cells by macrophages. (B) Tregs are recruited by chemokines and inhibit the action of cytotoxic T cells through immune checkpoints (e.g., CTLA-4 or GITR). Tregs release immunosuppressive cytokines such as TGF-β, IL-10, and IDO to inhibit dendritic cell function, disturbing a competent anti-tumor immune response. (C) MDSCs are also recruited by the CCL2/CCR2 axis in the GBM microenvironment and potently suppress anti-tumor immunity through PD1/PD-L1. MDSCs also deplete human essential amino acids, leading to impaired T-cell activation and function.